Field of the Invention
The present invention belongs to the field of biomedicine. More specifically, the present invention relates to compositions and methods for treating viral diseases.
Background Art
Hand foot and mouth disease (HFMD) is a common viral infection in Western Pacific regions and is a major cause of death and childhood disease in China and Asia. In 2011, there were two million children suffering from HFMD in Western Pacific regions (more than 1.6 million in China, more than 340,000 in Japan, and more than 11 million in Vietnam). In the past 20 years, epidemic outbreak occurred once every two to three years in summer and early autumn in countries having temperate climate (Solomon, Lewthwaite et al. 2010). Chinese mainland has had outbreaks every spring and summer since 2008.
HFMD mainly affects children under five. Major symptoms include mouth ulcers, hand, foot and mouth sores, mouth pain and burning (herpesangina). Most cases show only mild symptoms and are self-limiting. However, there are still a large number of cases (over twenty-seven thousand cases in China in 2010, about 1.6%), which showed severe neurological symptoms, such as aseptic meningitis, encephalitis and polio-like paralysis and central nervous system disorders and neurogenic pulmonary edema and cardiac dysfunction (Huang, Liu et al. 1999; Yang, Wang et al. 2009; Weng, Chen et al. 2010; Rhoades, Tabor-Godwin et al. 2011). 905 and 506 cases of deaths occurred in China in 2010 and 2011, respectively.
HFMD is caused by non-polio enteroviruses. Main pathogenic viruses responsible for HFMD outbreak in Anhui province in 2008 were EV71 and CVA16 (Yan, Gao et al.; Zhang, Wang et al. 2010; Zhu, Zhu et al. 2010). Majority of severe cases and deaths were caused by EV71 infection. EV71 C4 subtype is a major epidemic strain in China, whereas EV71 C1, C2, C4, B3, and B4 subtypes are prevalent in other regions of Asia (Yang, Ren et al. 2009).
HFMD spreads from patients to people by direct contact with mouth and nose discharges, blister fluids, and feces from infected persons (Solomon, Lewthwaite et al. 2010). Infected people are most contagious one week after disease onset, but contagiousness persists even after symptoms were improved (Han, Ma et al. 2010). Many infected people (including most infected adults) do not have symptoms. Children with oral rashes are easier to be diagnosed through clinical and follow-up virology diagnosis.
At present, no HFMD vaccines and drugs are available. The only way to treat patients and to prevent spreading has been hygiene, supportive care, pain relief, mouthwash, and intravenous immunoglobulin (Chinese Ministry of Health 2010). Although vaccines have been in development, protection efficiency, however, still remains unknown, and still requires long period of time for large-scale vaccination to be implemented.
Therefore, there is an urgent need to develop drugs that can prevent and treat HFMD in the field, especially, developing drugs that inhibit EV71 and CVA16 viral infection to achieve prevention and treatment from the source.